Organofluorine chemistry plays an important role in medicinal, agricultural, and material sciences and fields. Fluoroalkyl groups have strong effects such as high stability and lipophilicity, in addition, longer fluoroalkyl groups have high water and oil resistance and low fricition.
Loy, R. N., et al., Organic Letters 2011, 13, 2548-2551, discloses Pd-catalyzed coupling of CF3—I with benzene in 26% GC yield.
According to Table 1 entry 10 the coupling of C6F13I provided 81% yield. But a repetition of this experiment with the bromide instead of the iodide provided less than 1% yield, see Comparative Example 11 herein.
There was a need for homogenous catalyzed method for the preparation of fluoro, chloro and fluorochloro alkylated compounds by direct C—H trifluoromethylation, which provides high yields but does not need the assistance of a directing group or of electron rich aromatic compounds. The method should be applicable to a wide variety of substrates and should be compatible with a wide variety of functional groups. Furthermore the method should not be restricted to iodides as alkylating agents only, but should also work with other halides. And the method should work not only with perfluorinated alkyl iodides, but also with fluorinated, chlorinated and fluorochlorinated alkyl halides, especially for fluorinated alkyl halides.
Unexpectedly the presence of di(1-adamantyl)-n-butylphosphine and 2,2,6,6-tetramethylpiperidine 1-oxyl together with a soluble Pd based catalyst meets these requirements. No dialkylated products are observed.
In this text, the following meanings are used, if not otherwise stated:
Ac acetate;
alkyl linear or branched alkyl;
BuPAd2 CAS 321921-71-5, di(1-adamantyl)-n-butylphosphine;
DMSO dimethylsulfoxide;
eq, equiv equivalent;
halide F—, Cl—, Br— or I—, preferably Cl—, Br—, and I—, more preferably Br— and I—;
halogen F, Cl, Br or I; preferably F, Cl or Br; more preferably F or Cl;
“linear” and “n-” are used synonymously with respect to the respective isomers of alkanes;
MTBE methyl tert-butyl ether;
RT room temperature, it is used synonymously with the expression ambient temperature;
TEA triethylamine;
TEMPO CAS 2564-83-2,2,2,6,6-tetramethylpiperidine 1-oxyl;
TFA trifluoroacetate;
“wt%”, “% by weight” and “weight-%” are used synonymously and mean percent by weight.